Special Warning : אזהרת שימוש

4.4   Special warnings and precautions for use

Patients and their carers must be instructed that Abstral contains an active substance in an amount that can be fatal to a child, and therefore to keep all tablets out of the sight and reach of children.

Due to the potentially serious undesirable effects that can occur when taking an opioid therapy such as Abstral, patients and their carers should be made fully aware of the importance of taking Abstral correctly and what action to take should symptoms of overdose occur.

Before Abstral therapy is initiated, it is important that the patient’s long-acting opioid treatment used to control their persistent pain has been stabilised.

Opioid Use Disorder (abuse and dependence)
Tolerance and physical and/or psychological dependence may develop upon repeated administration of opioids such as fentanyl. Iatrogenic addiction following therapeutic use of opioids is known to occur.

Repeated use of Abstral may lead to Opioid Use Disorder (OUD). Abuse or intentional misuse of Abstral may result in overdose and/or death. The risk of developing OUD is increased in patients with a personal or a family history (parents or siblings) of substance use disorders (including alcohol use disorder), in current tobacco users or in patients with a personal history of other mental health disorders (e.g. major depression, anxiety and personality disorders).

Patients will require monitoring for signs of drug-seeking behaviour (e.g. too early requests for refills). This includes the review of concomitant opioids and psycho-active drugs (like benzodiazepines). For patients with signs and symptoms of OUD, consultation with an addiction specialist should be considered.

Respiratory Depression In common with all opioids, there is a risk of clinically significant respiratory depression associated with the use of Abstral. Particular caution should be exercised during dose titration with Abstral in patients with chronic obstructive pulmonary disease or other medical conditions predisposing them to respiratory depression (e.g. myasthenia gravis) because of the risk of further respiratory depression, which could lead to respiratory failure.

Increased intracranial pressure
Abstral should only be administered with extreme caution in patients who may be particularly susceptible to the intracranial effects of hyperkapnia, such as those showing evidence of raised intracranial pressure, reduced consciousness, coma or brain tumours. In patients with head injuries, the clinical course may be masked by the use of opioids. In such a case, opioids should be used only if absolutely necessary.

Hyperalgesia
As with other opioids, in case of insufficient pain control in response to an increased dose of fentanyl, the possibility of opioid-induced hyperalgesia should be considered. A fentanyl dose reduction or discontinuation of fentanyl treatment or treatment review may be indicated.

Cardiac disease
Fentanyl may produce bradycardia. Fentanyl should be used with caution in patients with previous or pre-existing bradyarrhythmias.

Elderly, cachectic or debilitated population
Data from intravenous studies with fentanyl suggest that older patients may have reduced clearance, a prolonged half-life and they may be more sensitive to the active substance than younger patients. Older, cachectic, or debilitated patients should be observed carefully for signs of fentanyl toxicity and the dose reduced if necessary.

Impaired hepatic or renal function
Abstral should be administered with caution to patients with liver or kidney dysfunction, especially during the titration phase. The use of Abstral in patients with hepatic or renal impairment may increase the bioavailability of fentanyl and decrease its systemic clearance, which could lead to accumulation and increased and prolonged opioid effects.

Hypovolaemia and hypotension
Care should be taken in treating patients with hypovolaemia and hypotension.

Use in patients with mouth wounds or mucositis
Abstral has not been studied in patients with mouth wounds or mucositis. There may be a risk of increased systemic drug exposure in such patients and therefore extra caution is recommended during dose titration.

Abstral withdrawal
There should be no noticeable effects on cessation of treatment with Abstral, but possible symptoms of withdrawal are anxiety, tremor, sweating, paleness, nausea and vomiting.

Serotonin Syndrome
Caution is advised when Abstral is co-administered with drugs that affect the serotoninergic neurotransmitter systems.

The development of a potentially life-threatening serotonin syndrome may occur with the concomitant use of serotonergic drugs such as Selective Serotonin Re-uptake Inhibitors (SSRIs) and Serotonin Norepinephrine Re-uptake Inhibitors (SNRIs), and with drugs which impair metabolism of serotonin (including Monoamine Oxidase Inhibitors [MAOIs]). This may occur within the recommended dose.

Serotonin syndrome may include mental-status changes (e.g., agitation, hallucinations, coma), autonomic instability (e.g., tachycardia, labile blood pressure, hyperthermia), neuromuscular abnormalities (e.g., hyperreflexia, incoordination, rigidity), and/or gastrointestinal symptoms (e.g., nausea, vomiting, diarrhoea).

If serotonin syndrome is suspected, treatment with Abstral should be discontinued.

Sleep-related breathing disorders
Opioids can cause sleep-related breathing disorders including central sleep apnoea (CSA) and sleep-related hypoxemia. Opioid use increases the risk of CSA in a dose-dependent fashion.
In patients who present with CSA, consider decreasing the total opioid dosage.

Risk from concomitant use of sedative medicines such as benzodiazepines or related drugs Concomitant use of Abstral and sedative medicines such as benzodiazepines or related drugs may result in sedation, respiratory depression, coma and death. Because of these risks, concomitant prescribing with these sedative medicines should be reserved for patients for whom alternative treatment options are not possible. If a decision is made to prescribe Abstral concomitantly with sedative medicines, the lowest effective dose should be used, and the duration of treatment should be as short as possible.
The patients should be followed closely for signs and symptoms of respiratory depression and sedation. In this respect, it is strongly recommended to inform patients and their caregivers to be aware of these symptoms (see section 4.5).

Abstral contains sodium
This medicine contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially ‘sodium-free’.

Effects on Driving

4.7     Effects on ability to drive and use machines

No studies on the effects on the ability to drive and use machines have been performed with Abstral.

However, opioid analgesics are known to impair the mental or physical ability to perform potentially hazardous tasks such as driving or operating machinery. Patients should be advised not to drive or operate machinery if they become dizzy or drowsy or experience blurred or double vision while taking Abstral.

This medicine can impair cognitive function and can affect a patient’s ability to drive safely.
When prescribing this medicine, patients should be told:

• The medicine is likely to affect your ability to drive
• Do not drive until you know how the medicine affects you